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EP3094251B1 - Dispositif de spectroscopie proche infrarouge et de spectroscopie de corrélation diffuse et méthodes associées - Google Patents

Dispositif de spectroscopie proche infrarouge et de spectroscopie de corrélation diffuse et méthodes associées Download PDF

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Publication number
EP3094251B1
EP3094251B1 EP15737911.6A EP15737911A EP3094251B1 EP 3094251 B1 EP3094251 B1 EP 3094251B1 EP 15737911 A EP15737911 A EP 15737911A EP 3094251 B1 EP3094251 B1 EP 3094251B1
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Prior art keywords
light
optical waveguide
cbf
wavelength
lights
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EP3094251A1 (fr
EP3094251A4 (fr
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Haruo Nakaji
Maria FRANCESCHINI
David Boas
Erin BUCKLEY
Pei-Yi Lin
Stefan Carp
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General Hospital Corp
Canon USA Inc
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General Hospital Corp
Canon USA Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14552—Details of sensors specially adapted therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14546—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • A61B5/14553—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases specially adapted for cerebral tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/40—Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4058—Detecting, measuring or recording for evaluating the nervous system for evaluating the central nervous system
    • A61B5/4064—Evaluating the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4866—Evaluating metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7225—Details of analogue processing, e.g. isolation amplifier, gain or sensitivity adjustment, filtering, baseline or drift compensation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271—Specific aspects of physiological measurement analysis
    • A61B5/7278—Artificial waveform generation or derivation, e.g. synthesizing signals from measured signals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
    • A61B2562/0238—Optical sensor arrangements for performing transmission measurements on body tissue

Definitions

  • This application relates generally to medical devices and methods and in particular to a device combining near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) and its use.
  • NIRS near-infrared spectroscopy
  • DCS diffuse correlation spectroscopy
  • NIRS Near infrared spectroscopy
  • SO2 oxygen saturation
  • SO2 is a surrogate for cerebral oxygen consumption
  • this measurement can provide information related to brain function through a quick and non-invasive route.
  • the oxygen saturation measured by NIRS may not highly correlate with brain functions compared with the cerebral oxygen consumption.
  • SO2 measurements are not always particularly sensitive when the measurements occur hours after brain injury occurs since oxygen consumption and delivery reach equilibrium after acute events.
  • CMRO 2 cerebral oxygen metabolism
  • the measurement procedure of the combined NIRS and DCS system includes measuring locations in frontal, temporal and adjacentntal areas of the patient's brain.
  • a process for this measurement is described by Lin, P. Y., et al., (J. Vis. Exp. (73), e4379, 2013 ).
  • the patient's hair was parted to expose a section of the patient scalp.
  • the probe was attached to the patient's head and the light sources and the detectors of the NIRS system were turned on.
  • the NIRS measurement was acquired for 16 seconds. After turning off the light sources and the detector of the NIRS system, the light source and the detectors of the DCS system were turned on.
  • Lin P.Y. et al.
  • the source and detector fibers for DCS were on the same probe as the NIRS source and detector fibers.
  • the DCS source and detector fibers were aligned separately and in a different location than the NIRS source and detector fibers. Therefore, the probe had to be slightly shifted before the DCS measurement in order to acquire the data at the same location on the patient's head.
  • the data of the DCS measurement was acquired for 10 seconds.
  • this process including taking both the NIRS and DCS measurements, was repeated three times at each of the chosen frontal, temporal and adjacentntal locations on the head.
  • This design does not allow simultaneous measurement of NIRS and DCS for several reasons, including that the probe must be shifted in order to measure at the same location and the fact that the NIRS and DCS detectors cannot discriminate between the different signals, requiring that both the source and the detector of the two technique are alternatively turned off when the measurements are obtained. Thus, the NIRS and DCS measurements cannot be operated simultaneously.
  • NIRS and DCS system were also reported by Peyman Zirak et al., (Biomedical Optics Express, Vol. 1, No. 5, pp. 1443-1456, 2010 ). This system described 0.5 seconds NIRS measurement followed by a 3 sec. DCS measurement, where measurements from two probes placed on either side of a forehead were carried out simultaneously. In each probe, the line between the NIRS source and detector fibers in the probe was crossed with the line between the DCS source and detector fibers so that the measurements were carried out at roughly the same tissue volume. However, the area including all fibers was quite large. Thus, the probe as described by Peyman Zirak et al.
  • a sophisticated method to quantify cerebral oxygen metabolism is needed.
  • Such a system would provide quantifiable results with improved detection of, for example, brain health, brain development, and response to therapy and particularly to for improved detection in neonates.
  • this system would be more usable by a physician or technician.
  • an apparatus and method for reducing acquisition time and the need for either several instruments or the need to turn different sources and detectors on and off while performing the method There is further a need for an apparatus that can take NIRS and DCS measurements simultaneously.
  • an integrated device according to claim 1.
  • the present invention provides an apparatus and method for the combination of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS).
  • NIRS near-infrared spectroscopy
  • DCS diffuse correlation spectroscopy
  • NIRS Near-infrared spectroscopy
  • Hemoglobin is the oxygen-transport metalloprotein in the blood cells. Hemoglobin picks up oxygen in the lungs then carries the oxygen from the lungs to the tissues and releases it. Oxyhemoglobin is hemoglobin having an additional oxygen molecule. Deoxyhemoglobin is hemoglobin that is not combined with oxygen.
  • Red blood cells will contain different concentrations of oxyhemoglobin and deoxyhemoglobin.
  • the absorption spectrum of the blood reflects this difference in concentration.
  • the NIRS system measures the oxygen saturation by utilizing the absorption spectra of oxyhemoglobin and deoxyhemoglobin. Since the absorption spectrum of oxyhemoglobin in the near-infrared wavelength region is different from that of deoxyhemoglobin (see FIG.
  • a wavelength range from about 660 nm to about 910 nm is particularly useful in distinguishing the different concentrations of oxyhemoglobin and deoxyhemoglobin and then determining oxygen content in blood.
  • a wavelength range of 660 nm to about 830 nm is also particularly contemplated. While it is possible to use wavelengths outside the wavelength range from about 660 nm to about 910, nm such as between 250 nm and 1.5 ⁇ m.
  • detectors such as PMT detectors have reduced efficiency at collecting the scattered light. Therefore, unless a detector with greater IR efficiency is used, the use of longer wavelengths is not preferred.
  • NIRS In order to measure the absorption spectrum of blood using NIRS, it is preferable to use multiple wavelength light source(s). For example, eight laser diodes having eight different wavelengths were used by Lin P. Y., et al. In another experiment, Grant, P. E. et al., (J. Cerebral Blood Flow & Metab. (2009) 29, 1704-1713 ) used eight wavelengths and eight laser diodes having different wavelengths from each other to measure the absorption spectrum of blood.
  • Source-detector distances can be used to quantify absorption and scattering coefficients with this system.
  • These source-detector separations may be chosen to optimize the depth of penetration of the NIR radiation. For example, source-detector separations of 1 cm, 1.5 cm, 2 cm, and 2.5 cm are chosen to quantify absorption and scattering coefficients, which includes the cerebral cortex in neonates. In other examples, source-detector separations of, for example, two or more of 1.5 cm, 2 cm, 2.5 cm, 3.0 cm, 3.5 cm, and 4.0 cm are chosen. In some embodiments, a source-detector separation of 3.0 cm or less is preferred. In other embodiments, fewer or more source-detector separations are used to perform NIRS.
  • the absorption coefficients ( ⁇ a ( ⁇ )) of the blood at each chosen wavelength are calculated from the power of the SO2 light coming from the tissue 306 and the power of the SO2 light incident on the tissue 306.
  • ⁇ a ( ⁇ ) is a blood absorption coefficient as a function of wavelength
  • ⁇ ⁇ xy -( ⁇ ) and ⁇ deoxy -( ⁇ ) are absorption coefficients of oxyhemoglobin and deoxy
  • the oxygen saturation is determined using NIRS.
  • CMRO 2 cerebral metabolic rate of oxygen
  • St02 cerebral metabolic rate of oxygen
  • DCS cerebral metabolic rate of oxygen
  • the NIRS system measures the oxygen saturation in the tissue.
  • DCS system measures the velocity of blood flow.
  • DCS measures speckle fluctuations of near-infrared diffuse light in the tissue where the speckle fluctuation depends on the motions of red blood cells.
  • DCS can non-invasively measure the velocity of blood flow in the deep tissue and thus provide the cerebral blood flow index (CBFi). While DCS measures the effective Brownian diffusive coefficient. Although the unit of the effective Brownian diffusive coefficient is different from the unit of blood flow, the change in that correlates with the change in blood flow [Boas, 2011]. Thus, for measurements of blood in capillary instead of in the artery or vein, the cross-section is unlikely to change since, in general, capillaries do not have smooth muscle. DCS measurements are described, for example, in U.S. Pat. No. 6,076,010 .
  • CMRO2 blood flow measured from sources other than the cerebral cortex, such as from the pial veins found above the cortex is accounted for in the calculation of CMRO2.
  • a correction factor may be used to remove pial contamination of the signal to obtain a more accurate cerebral blood flow measurement.
  • the relative content of cerebral and pial or other blood flow may be attributed to measurements at different source-detector separations and the non-cerebral concentrations and this consideration taken into account when calculating CMRO2. See Strangeman, Li, and Zhang, (201) PLOS One, 8(8) e66319.
  • the devices and methods provided herein are particularly advantageous in that they allow for the determination of oxygen consumption that can be more accurate calculated than previously determined by using data obtained from measurements of both NIRS and DCS.
  • Oxygen consumption is determined using hemoglobin concentration, blood flow index, arterial oxygenation, and tissue oxygenation.
  • tissue oxygenation is determined by NIRS measurements and blood flow index is determined with DCS measurements. Additional systemic parameters can also be used in determining oxygen consumption.
  • Hemoglobin concentration which can be determined by a blood test and arterial oxygenation which can be determined using a pulse oxymeter are also measured
  • HGB the hemoglobin concentration measured by a blood test
  • Sa02 the arterial oxygen saturation (oxygenation) measured by a pulse oxymeter
  • St02 the tissue oxygen saturation measured by NIRS
  • ⁇ ( ⁇ 0.84) is the percent contribution of the venous compartment to the hemoglobin oxygenation measurement.
  • CBFi is the cerebral blood flow index measured by DCS. Therefore, by combining the NIRS measurement of St02 and the DCS measurement of CBF i , CMRO 2 can be estimated. See Lin P. Y. et al., J Vis Exp (73): e4379 .
  • FIG. 3A shows an exemplary embodiment of the combined NIRS and DCS system (300).
  • eight laser diodes (302) having eight different wavelengths are used for the NIRS measurement.
  • the light output from the multiple wavelength light source(s) (302) is delivered via an optical fiber (304) where it connects to the tissue (306) through the probe tip (308).
  • the light radiated to the tissue (306) is scattered in the tissue.
  • a part of the scattered light is collected by the optical fiber (310) at the probe tip (308) and input to the photomultiplier tube used as the NIRS detector (312) after passing through an optional lense system that includes collimating lenses (314) and a low pass filter (316).
  • the light source for the DCS measurement (322) as exemplified in FIG. 3A is different from that for the NIRS measurement.
  • the coherent length of the DCS laser source (322) is long, because the DCS measurement utilizes the interference of multiply scattering light.
  • the light emitted from the DCS light source (CBF light source (322) is delivered by the optical fiber (324).
  • the CBF light is radiated to the tissue (306) and scattered into the tissue.
  • a part of the scattered CBF light is collected by the optical fiber (326) and input to the avalanche photodiode detector (APD) for the DCS measurement (328).
  • the light path includes a lense system that contains collimating lenses (330) and a high pass filter (332).
  • the scattered SO2 light inputs into both the optical fibers (310) and (326).
  • the scattered CBF light inputs into both the optical fibers (310) and (326).
  • the filter in front of the PMT (316) passes through only SO2 signal, attenuate the intensity of CBF light.
  • only SO2 light is input to the PMT in the embodiment shown in FIG. 3A . If the filter (332) is put in front of the APD, that filter (332) passes through only CBF light and attenuate the intensity of SO2 light. As a result, only CBF light is input to the APD. Therefore, it is not necessary to turn off the light source of DCS while the NIRS light source is turned on.
  • CMRO 2 is calculated from the oxygen saturation measured by NIRS and the blood flow measured by DCS. In order to do that, the probe configuration is important.
  • the computer system 350 includes CPU 351, Storage/RAM 352, I/O Interface 353 and Detector Interface 354. Also, Computer system 350 may comprise one or more devices.
  • the one computer may include components 351, 352 and 353 and other computer may include component 354.
  • the CPU 351 is configured to read and perform computer-executable instructions stored in the Storage/RAM 352.
  • the computer-executable instructions may include those for the performance of the methods and/or calculations described herein.
  • CPU 351 calculates speckle fluctuations of near-infrared diffuse light as temporal intensity fluctuations based on the detected light by the detector for the CBF light.
  • CPU 351 calculates CMRO2, as oxygen consumption, using data obtained from analyzing the SO2 lights and the CBF light.
  • Storage/RAM 352 includes one or more computer readable and/or writable media, and may include, for example, a magnetic disc (e.g., a hard disk), an optical disc (e.g., a DVD, a Blu-ray), a magneto-optical disk, semiconductor memory (e.g., a non-volatile memory card, flash memory, a solid state drive, SRAM, DRAM), an EPROM, an EEPROM, etc.
  • Storage/RAM 352 may store computer-readable data and/or computer-executable instructions. The components of the computer system 350 communicate via a bus.
  • the I/O interface 353 provides communication interfaces to input and output devices, which may include a keyboard, a display, a mouse, a printing device, a touch screen, a light pen, an optical storage device, a scanner, a microphone, a camera, a drive, communication cable and a network (either wired or wireless).
  • input and output devices may include a keyboard, a display, a mouse, a printing device, a touch screen, a light pen, an optical storage device, a scanner, a microphone, a camera, a drive, communication cable and a network (either wired or wireless).
  • the detector interface 354 also provides communication interfaces to input and output devices, which may include photomultiplier tube (PMT) 312, an avalanche photodiode detector (APD) 328. Also, the function of detector may be realized by computer executable instructions (e.g., one or more programs) recorded on a Storage/RAM 352.
  • PMT photomultiplier tube
  • APD avalanche photodiode detector
  • the function of detector may be realized by computer executable instructions (e.g., one or more programs) recorded on a Storage/RAM 352.
  • FIG. 4 shows the tip of the probe (40) described by in Lin et al.
  • the surface shown in FIG. 4 is placed on the head.
  • the feature of the arrangement of fibers shown in FIG. 4 is that the NIRS source (41) and detector fibers (42) are aligned in the different line from the NIRS source (43) and detector fibers (44). Therefore, in order to acquire the data at the same location, the probe is slightly shifted since the NIRS line (45) and DCS line (46) are physically separated. In this embodiment, the separation is approximately 5 mm. Thus, for any measurements where the NIRS and DCS measurements are taken at the same location and the NIRS and DCS measurements cannot be operated simultaneously.
  • FIG. 5 shows the probe used by Peyman Zirak et al (50).
  • the line (55) between the NIRS source (51) and detector fibers (52) is crossed the line (56) between the DCS source (53) and detector fibers (54).
  • three laser sources were combined in one fiber bundle (51) and two NIRS detectors (52) are used with a single source-detector separation of 2.5 cm (55).
  • Two probes according to FIG. 5 were placed symmetrically on the forehead of adult patients to measure oxyhemoglobin and deoxyhemoglobin concentrations.
  • the probe shown in either previously disclosed FIG. 4 or FIG. 5 it is difficult to apply the probe shown in either previously disclosed FIG. 4 or FIG. 5 to a part with the hair. Hair scatters the light strongly. Thus, if hair is inserted between the optical fiber and the tissue, the power of the light is decreased and the efficacy of the measurement is decreased.
  • the patient's hair is preferably combed to a part where the probe is attached to the scalp. However, the area of the scalp thus exposed by the part is narrow. Therefore, the probe area including all fibers should also be narrow. With a narrow probe, the probe may be placed on the head and both NIRS and DCS measurements may be taken, either simultaneously or sequentially, without the need to adjust the probe position.
  • the optical fibers for light radiation and detection for both NIRS and DCS are arranged in the single line.
  • an exemplary probe is shown for the combination of NIRS and DCS that is particularly useful for simultaneous measurements.
  • the linear arrangement between each of the source and detector probes is shown.
  • the DCS source (602) is in line with the DCS detector (608)
  • the NIRS sources (606) are in line with the NIRS detector (604)
  • both the NIRS and DCS sources and detectors are found on a single linear line (610).
  • the DCS source/detector pair spacing, L5, is also shown and, is 20 mm in one example.
  • FIG. 7 shows another embodiment for the combination of NIRS and DCS that is particularly useful for simultaneous measurements.
  • the linear arrangement between each of the four probes is shown.
  • the DCS source (702) is in line with the DCS detector (708)
  • the NIRS sources (706) are in line with the NIRS detector (704) and both the NIRS and DCS sources and detectors are found on a single linear line (710).
  • FIG. 8 shows yet another embodiment for the combination of NIRS and DCS having a linear arrangement between each of the probes.
  • the DCS source (802) is in line with the DCS detector (808)
  • the NIRS sources (806) are in line with the NIRS detector (804) and both the NIRS and DCS sources and detectors are found on a single linear line (810).
  • the probe exemplified in FIG. 8 has dimensions of 4 x 1.5 x 2 cm.
  • the various optical fibers are aligned linearly, and arranged such that they substantially form a line.
  • the location of the different optical fibers onto the probe tip is determined as follows: first, select the optical fiber having the widest diameter. Then, draw a line between the centers of the optical fiber having the widest diameter (d wide ) and the optical fiber which make a pair with the optical fiber having the widest diameter. For example, if the diameter of the NIRS detector fiber is the widest, the line between the centers of the NIRS detector and source fibers is drawn. The distal ends of each of the other fibers are placed on the probe tip in a linear arrangement and are at a location such that they are placed on or near this line.
  • the probe body contains fiber bundles that are bent at 90 degree angles. In other embodiments, the fiber bundles are bent at more or less than 90 degrees, such as at greater than 45 degrees.
  • each of the optical fibers is arranged so that the fibers are aligned linearly (they substantially form a line).
  • Each of the optical fibers may be centered or substantially centered on the line described above.
  • the different optical fibers may be offset from the center line but still lay on a line that is defined as having a line width as wide as the widest diameter fiber optic.
  • the maximum offset from the center of the line for a fiber having a diameter D2 is 1 ⁇ 2(d wide -d 2 ).
  • the optical fibers may be offset from the center line of the line described above such that at least half of the fiber area is within the line width.
  • the maximum offset from the center of the line for a fiber having a diameter d2 is 1 ⁇ 2d wide .
  • a probe tip that is configured such that the DCS and NIRS sources and the DCS and NIRS detectors are at the same location is an optimal configuration from the perspective of sampling the tissue. While realizing this design can be challenging from the instrument configuration perspective, the present disclosure provides an optimal means for making a probe tip having this configuration using the filtering strategy wherein the DCS wavelength (e.g., the third wavelength) is either longer or shorter than the NIRS wavelengths (e.g., at least the first and second wavelengths). In some embodiments, one or more, or even all of the optical waveguides are bent near the probe tip. This can provide easier fabrication.
  • the probe tip has a substantially flat surface that interfaces with the tissue sample. This allows for more accurate sampling.
  • the probe may be designed such that the waveguides, which may be optical fibers, exit from the side of the probe at approximately 90 degrees to maintain a low probe profile when placed against the head or other tissue.
  • the first and second waveguides are located at discreet distances from the fourth optical waveguide.
  • the first waveguide is located discreet distance from both the fourth optical waveguide and an additional waveguide configured to transmit SO2 lights scattered from tissue.
  • Each of the first and second waveguides (and optionally further waveguides) may transmit a single or multiple wavelengths of light.
  • the first and second waveguides are located at discreet distances from the fourth optical waveguide and from at least one additional waveguide that is configured to transmit SO2 lights scattered from the tissue.
  • Each of the first and second waveguides (and optionally further waveguides), may transmit a single or multiple wavelengths of light.
  • there is a fifth optical waveguide and an additional optical waveguide configured to transmit the CBF light scattered from the tissue that are at different discreet distances from the third optical waveguide at the probe tip.
  • there is an additional optical waveguide configured to deliver a CBF light towards the tissue, wherein this additional optical waveguide is located at a different source-detector distance than the distance between the third and fifth waveguides at the probe tip.
  • the present invention provides an advantage over the known art in that NIRS and DCS measurements can be operated at the same location simultaneously and there is no need to move the probe between NIRS and DCS measurements.
  • both the NIRS and DCS portions may be calibrated without moving the probe, and may be calibrated simultaneously.
  • source-detector separations may be chosen to optimize the various depths of penetration for the DCS measurement.
  • source-detector separations of, for example 1.5 cm, 2 cm, 2.5 cm, 3.0 cm, 3.5 cm, and 4.0 cm are chosen.
  • a source-detector separation of 3.0 cm or less is preferred.
  • the integrated device includes an optical scatterer between the distal end of the third optical fiber and probe tip. This is particularly useful to attenuate the CBF light to a level that is safe for continued exposure on skin.
  • An exemplary optical scatterer is piece of Teflon® such as a thin Teflon® disk.
  • the incident power of CBF light to the tissue is higher than that of the SO2 light.
  • the incident power of SO2 light to the tissue is about 3 mW and that of CBF light is about 20 mW.
  • the SO2 light is modulated at, for example, a frequency of 110 MHZ.
  • CMRO 2 is estimated from St02 measured by NIRS and CBF; measured by DCS.
  • St02 and CBF i should be measured simultaneously.
  • the wavelength used for DCS measurements was set within the NIRS range (S02 light). Therefore, it is impossible to measure both DCS and NIRS at the same time.
  • the wavelength of CBF light is set out of the SO2 light wavelength range.
  • the wavelength of CBF light may be greater than or shorter than the wavelengths of each of the SO2 lights.
  • the CBF light is separated from the SO2 light and is at a longer wavelength than each of the NIRS wavelengths.
  • the wavelengths of eight SO2 lights are 660, 670, 690, 705, 730, 780, 808, and 830 nm and the wavelength of CBF light is 850 nm.
  • the wavelength of the CBF light is 670 nm and the SO2 lights are at 690, 705, 730, 780, 808, and 830 nm.
  • fewer or more SO2 lights may be used.
  • the eight SO2 lights come from eight SO2 sources. Alternatively, fewer sources may be used.
  • the CBF light has a wavelength that is greater than the wavelengths SO2 light. This is particularly advantageous since, as DCS generally uses a single mode fiber, much less light can be coupled into the detection fiber. Thus, it is advantageous to select a wavelength with greater scattering efficiency for the CBF light, or longer wavelength light.
  • An optical filter may be placed in front of the detector for NIRS measurement to attenuate the CBF light in order to prevent the CBF light from substantially affecting the NIRS measurement.
  • a low pass filter blocking light at 850 nm and above may be used.
  • a notch filter may be used.
  • an optical filter may be placed in front of the detector for DCS measurement to attenuate SO2 light at one or more of the NIRS wavelengths in order to prevent the SO2 light from substantially affecting the DCS measurement.
  • the signal is filtered using signal processing.
  • the device does not contain a filter located between the probe tip and the DCS detector.
  • This embodiment is particularly useful in instances where the light intensity of the CBF light is large compared to the light intensity of each of the SO2 lights.
  • the CBF light is at least 10-fold more powerful than any of the SO2 light and a filter blocking the CBF light is found in front of the detector set to analyze SO2 light and no filter is found in front of the detector set to analyze CBF light.
  • the term "substantially,” when used in context of substantially attenuating light, means that the intensity of the light is decreased by at least 70%, or more preferably at least 80%, or more preferably at least 85%, or more preferably at least 50%, or more preferably at least 95%, or more preferably at least 97%, or more preferably at least 99%.
  • the integrated device comprises a first and a second waveguide, each delivering at least one SO2 light to the tissue.
  • the device may comprise a fiber bundle where the two different wavelengths are delivered via two different fibers in a fiber bundle. Multiple additional wavelengths of SO2 light may also be delivered via fibers in the fiber bundle.
  • both the first and second waveguides deliver at least two wavelengths, where the two waveguides may both transmit the same wavelengths.
  • the first waveguide transmits four wavelengths within the range of 660 and 910 nm and the second waveguide transmits four wavelengths within the range of 660 and 910 nm, where there are eight unique NIRS wavelengths.
  • the first waveguide transmits four wavelengths within the range of 660 and 910 nm and the second waveguide transmits the same four wavelengths.
  • each waveguide delivers 3, 5, 6, 7, or 8 different wavelengths.
  • the integrated device comprises a first waveguide configured to deliver at least two SO2 lights to the tissue.
  • the two different wavelengths of light can be combined into a single waveguide via an optical splitter or coupler, an optical combiner, an optical switch, or by any other means known in the art to combine two or more different wavelengths into a single optical waveguide.
  • FIG. 3 shows the schematic diagram of NIRS and DCS measurement system.
  • Eight SO2 lights are emitted from the laser diodes and incident to the tissues via an optical fiber bundle.
  • the laser system with the long coherent length is used for a DCS laser source.
  • the CBF light is incident to the tissue via an optical fiber. Those lights are scattered in the tissue.
  • a part of the scattered SO2 light is collected by an optical fiber light guide.
  • the optical shortpass filter is inserted between the optical fiber light guide and a PMT in order to attenuate the CBF light.
  • the cutoff wavelength of the shortpass filter is set between the wavelengths of the SO2 light at the longest wavelength and the CBF light.
  • a part of the scattered CBF light is collected by a single mode fiber.
  • the optical longpass filter may be inserted between the single mode fiber and the APD in order to attenuate the SO2 lights.
  • the cutoff wavelength of the longpass filter is set between the wavelengths of the SO2 light at the longest wavelength and the CBF light. If the incident power of CBF light is higher than that of SO2 light sufficiently, the optical longpass filter in front of APD for DCS measurement may not be needed.
  • the wavelength of CBF light is arranged out of the NIRS wavelength range. In one embodiment, the wavelength of the CBF light is longer than the wavelengths of SO2 lights.
  • a filter used for eliminating unwanted light from the DCS excitation source is put in front of the detector for NIRS in order to prevent light from the DCS excitation or scatter to hit the detector(s) for the SO2 light.
  • This filter may be, for example an optical shortpass filter.
  • the cutoff wavelength of the optical shortpass filter is set between the longest wavelength of SO2 light and the wavelength of CBF light.
  • Hemoglobin concentration can be measured by any means known in the art, such as by a standard blood test. [HGB] is among the most commonly performed blood tests and is usually part of a complete blood count.
  • Sa02 is the arterial oxygenation, or arterial oxygen saturation.
  • SaO2 provides percentage of hemoglobin binding sites in the bloodstream that are occupied by oxygen. This variable can be measured by any means known in the art.
  • a pulsed oxymeter is used.
  • a pulse oxymeter measures the light absorption characteristics of saturated hemoglobin to measure oxygen saturation.
  • the pulsed oxymeter may be integrated into the device as described herein or it may be a separate device commonly used by doctors and technicians.
  • simultaneous when used in connection with simultaneously measuring means that the measurements are taken within the span of a single heartbeat and thus within the span of substantive change in oxygenation.
  • simultaneous means less than 5 sec., less than 4 sec., less than 3 sec., less than 2 sec., less than 1 sec., less than 500 msec., or less than 200 msec.
  • simultaneous measurements mean that both the SO2 light and the CBF light are incident on the tissue of a subject at the same time where the CBF light does not have to be blocked or turned off in order to perform a measurement using the SO2 light and vice versa.
  • simultaneous detection means that the first detector detects light at the first and/or second wavelengths at the same time that the second detector detects light at the third wavelength. This can be done without switching the CBF light off.
  • simultaneous includes embodiments where both the CBF light source and the SO2 light source are turned on at the same time.
  • the light transmitted from a substrate such as a tissue that is described herein is only a quantity of the total scattered and/or reflected light. Much of the total scattered and/or reflected light will not be captured by the apparatus as described herein and is not measured.
  • temporal resolution refers to the precision of a measurement with respect to time. Oxygen saturation and blood flow vary over time. In order to estimate more exact oxygen consumption, oxygen saturation should be measured at the same time with the blood flow. Employing this invention, the temporal resolution can be decrease compared with that shown by Lin et al.
  • the phrase "greater than the peak intensities” means that the value is greater than the average of the peak intensities, not any instantaneous peak intensity. It is understood that fluctuations may occur in the signal intensity and that such fluctuations may be smoothed to provide a more stable value for peak intensity.
  • spatially relative terms such as “under” “beneath”, “below”, “lower”, “above”, “upper”, “proximal”, “distal”, and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the various figures. It should be understood, however, that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, a relative spatial term such as “below” can encompass both an orientation of above and below.
  • the device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein are to be interpreted accordingly. Similarly, the relative spatial terms “proximal” and “distal” may also be interchangeable, where applicable.
  • first, second, third, etc. may be used herein to describe various elements, components, regions, parts and/or sections. It should be understood that these elements, components, regions, parts and/or sections should not be limited by these terms. These terms have been used only to distinguish one element, component, region, part, or section from another region, part, or section. Thus, a first element, component, region, part, or section discussed below could be termed a second element, component, region, part, or section without departing from the teachings herein.
  • a hybrid FDNIRS-DCS instrument was built having dimensions of approximately 23" (1) x 18" (w) x 9" (h).
  • the FDNIRS portion of the instrument has 16 radio frequency (110 MHz) modulated laser diodes operating at 8 different wavelengths ranging from 670-830 nm and two photomultiplier tube detectors (PMT) for heterodyne detection (similar to the Imagent from ISS, Inc).
  • the DCS component of the instrument has a long-coherence length 852 nm laser, 4 low dark-count photon counting avalanche photodiodes, and a custom-made 256-tau correlator board.
  • a notch filter was placed in front of the FDNIRS PMTs.
  • the probe body in this embodiment contained four FDNIRS fiber bundles bent at 90 degree angles and providing four source-detector separations for FDNIRS (1.5, 2.0, 2.5, and 3.0 cm).
  • FDNIRS FDNIRS
  • 2 right angle prisms separated by 2.0 cm may be used to deliver and collect light to/from the tissue surface.
  • four single mode fibers are bundled together and their signals are averaged to improve the signal-to-noise ratio.
  • the FDNIRS component has a dynamic range of 35 dB (10log10, presuming the FDNIRS voltage is proportional to the optical power).
  • the minimum detection limit is 0.032 pW/ ⁇ Hz with 0.35°/ ⁇ Hz phase noise at a signal level of 10 pW.
  • the AC amplitude is stable to within 0.7% and the phase is stable to within 0.2°.

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Claims (17)

  1. Dispositif intégré qui combine la détection du changement de saturation d'oxygène (S02) par spectroscopie proche de l'infrarouge (NIRS) et le débit sanguin cérébral (CBF) par spectroscopie par corrélation diffuse (DCS) qui comprend :
    un premier guide d'onde optique (304) configuré pour délivrer une lumière à une première longueur d'onde vers un tissu (306) ;
    et dans lequel le premier guide d'onde optique est configuré pour délivrer une lumière à une seconde longueur d'onde vers le tissu, ou où le dispositif contient un second guide d'onde optique configuré pour délivrer la lumière à la seconde longueur d'onde vers le tissu,
    dans lequel chacune des lumières de la première et de la seconde longueurs d'onde est désignée « lumière SO2 » ;
    un troisième guide d'onde optique (324) configuré pour délivrer une lumière à une troisième longueur d'onde qui est différente des longueurs d'onde de la lumière SO2 vers le tissu, la lumière à la troisième longueur d'onde étant désignée « lumière CBF », et où la troisième longueur d'onde est soit plus longue, soit plus courte que chacune des longueurs d'onde des lumières SO2 ;
    un quatrième guide d'onde optique (310) configuré pour transmettre une ou plusieurs des lumières SO2 diffusées par le tissu ;
    un cinquième guide d'onde optique (326) configuré pour transmettre la lumière CBF diffusée par le tissu ;
    une extrémité de sonde reliée à l'extrémité distale de chacun du premier, du second, du troisième, du quatrième et du cinquième guides d'onde optiques, et du second guide d'onde optique si le dispositif intégré comprend le second guide d'onde optique, où les extrémités distales de tous ces guides d'onde sont alignées linéairement dans une zone de sonde étroite à l'extrémité de la sonde ;
    un premier détecteur (312), en communication optique avec le quatrième guide d'onde optique, configuré pour détecter les lumières SO2 ;
    un second détecteur (328) en communication optique avec le cinquième guide d'onde optique, configuré pour détecter la lumière CBF diffusée par le tissu ;
    un premier filtre (316) situé en face du premier détecteur, où le premier filtre permet aux lumières SO2 de passer au travers et atténue sensiblement la lumière CBF ;
    où le dispositif intégré est configuré pour détecter les lumières SO2 et CBF en même temps.
  2. Dispositif intégré selon la revendication 1, dans lequel la troisième longueur d'onde est plus longue que la première longueur d'onde et la seconde longueur d'onde, et/ou dans lequel la troisième longueur d'onde est plus longue que la première longueur d'onde et la seconde longueur d'onde, et
    la troisième longueur d'onde est séparée de la plus longue de la première longueur et de la seconde longueur d'onde d'au moins 10 nm.
  3. Dispositif intégré selon la revendication 2, comprenant en outre un second filtre situé en face du second détecteur, dans lequel le second filtre permet à la lumière CBF de passer au travers et atténue sensiblement les lumières S02.
  4. Dispositif intégré selon la revendication 1 comprenant le second guide d'onde optique, dans lequel le premier guide d'onde optique et le second guide d'onde optique sont configurés pour délivrer au moins deux longueurs d'onde différentes de lumière vers le tissu.
  5. Dispositif intégré selon la revendication 1 comprenant le second guide d'onde optique, dans lequel le second guide d'onde optique est configuré pour délivrer des lumières aux mêmes longueurs d'onde que celles délivrées par le premier guide d'onde optique.
  6. Dispositif intégré selon la revendication 1, dans lequel le premier guide d'onde est configuré pour délivrer une lumière à au moins huit longueurs d'onde.
  7. Dispositif intégré selon la revendication 6 comprenant le second guide d'onde, dans lequel le second guide d'onde est configuré pour délivrer une lumière à au moins huit longueurs d'onde qui sont identiques à ou différentes des huit longueurs d'onde délivrées par la première fibre.
  8. Dispositif intégré selon la revendication 6, comprenant en outre un sixième guide d'onde optique configuré pour transmettre une ou plusieurs lumières SO2 diffusées par le tissu et un troisième détecteur en communication optique avec le sixième guide d'onde optique.
  9. Dispositif intégré selon la revendication 1, dans lequel le premier, et les troisième au cinquième guides d'onde optiques et, le cas échéant, le second guide d'onde optique sont un guide d'onde optique respectif, une ligne centrale à l'extrémité de la sonde est définie comme se trouvant entre le centre du guide d'onde optique ayant le plus grand diamètre dwide et le guide d'onde optique qui crée une paire de source/détecteur avec le guide d'onde optique qui possède le diamètre dwide, et dans lequel un écart maximal entre la ligne centrale et le premier, le second, le troisième, le quatrième et le cinquième guides d'onde optiques est égal ou inférieur à 1/2 dwide.
  10. Dispositif intégré selon la revendication 1, dans lequel la séparation entre l'extrémité distale du premier guide d'onde optique et l'extrémité distale du quatrième guide d'onde optique et la séparation entre l'extrémité distale du troisième guide d'onde optique et l'extrémité distale du cinquième guide d'onde optique sont choisies afin d'optimiser la profondeur de pénétration de la lumière diffusée ayant une longueur d'onde comprise entre 660 et 910 nm.
  11. Dispositif intégré selon la revendication 1, dans lequel la séparation entre l'extrémité distale du premier guide d'onde optique et l'extrémité distale du quatrième guide d'onde optique est au maximum de 4 cm, et dans lequel la séparation entre l'extrémité distale du troisième guide d'onde optique et l'extrémité distale du cinquième guide d'onde optique est au maximum de 4 cm.
  12. Dispositif intégré selon la revendication 1, où le dispositif intégré est conçu pour permettre une détection au niveau du premier détecteur lorsque la lumière CBF est allumée.
  13. Dispositif intégré selon la revendication 1 comprenant en outre un processeur conçu pour quantifier les fluctuations d'intensité temporelle au sein de la lumière détectée par le second détecteur, dans lequel le processeur est capable de déterminer la consommation d'oxygène en utilisant les données obtenues à partir de l'analyse des lumières SO2 et de la lumière CBF.
  14. Dispositif intégré selon la revendication 13, dans lequel la consommation d'oxygène CMRO2 est déterminée à l'aide des paramètres suivants :
    la concentration en hémoglobine, déterminée par un test sanguin,
    l'indice de débit sanguin, déterminé en mesurant la lumière CBF,
    l'oxygénation artérielle, déterminée à l'aide d'un oxymètre de pouls, et
    l'oxygénation tissulaire, déterminée en mesurant les lumières SO2.
  15. Dispositif intégré selon la revendication 13, dans lequel la consommation d'oxygène CMRO2 est déterminée à l'aide de l'équation : CMRO 2 = HGB × CBF i × SaO 2 − StO 2 4 × MW Hb × β
    Figure imgb0011
     ou dans lequel la consommation d'oxygène relative rCMRO2 est déterminée à l'aide de l'équation : rCMRO 2 = CMRO 2 CMRO 2 o = HGB HGB o ⋅ CBF i CBF io ⋅ SaO 2 − StO 2 SaO 2 o − StO 2 o
    Figure imgb0012
     où :
    HGB correspond à la concentration en hémoglobine,
    CBFi correspond à l'indice de débit sanguin cérébral,
    SaO2 correspond à la saturation d'oxygène artérielle,
    StO2 correspond à la saturation d'oxygène tissulaire,
    MWhb correspond au poids moléculaire de l'hémoglobine,
    β correspond au pourcentage de concentration du compartiment veineux par rapport à la mesure d'oxygénation de l'hémoglobine, et
    l'indice « o » correspond à une référence.
  16. Dispositif intégré selon la revendication 15, où :
    la lumière CBF présente une intensité lumineuse moyenne supérieure aux intensités lumineuses moyennes des lumières SO2 ;
    le dispositif intégré comprend une première source de lumière, ayant au moins la première longueur d'onde comprise entre 660 et 910 nm et la seconde longueur d'onde comprise entre 660 et 910 nm adaptée pour délivrer les lumières SO2 au premier guide d'onde et, le cas échéant, au second guide d'onde,
    dans lequel la première source de lumière comprend une pluralité de diodes laser et la seconde source de lumière comprend un laser ; et/ou
    le dispositif comprend en outre une sonde adaptée pour mesurer StO2 et une sonde adaptée pour mesurer CBFi.
  17. Procédé de mesure simultanée de l'oxygénation tissulaire cérébrale StO2 et l'indice de débit sanguin cérébral CBFi dans un tissu (306) d'un sujet à l'aide du dispositif selon l'une quelconque des revendications 1 à 16, qui comprend les étapes consistant en :
    la détermination du StO2 dans le tissu du sujet comprenant les étapes consistant à :
    transmettre au moins deux lumières, ayant au moins deux longueurs d'onde différentes comprises entre 660 et 910 nm, au tissu, où les au moins deux lumières sont désignées « lumières SO2 »,
    détecter les lumières SO2 après qu'elles se sont déplacées à travers le tissu, avec un premier détecteur (312), et
    déterminer la différence entre l'intensité des lumières SO2 transmises et les lumières SO2 détectées à chacune des au moins deux longueurs d'onde différentes, et
    déterminer la différence d'atténuation afin d'obtenir le StO2 ;
    la détermination du CBFi dans le tissu du sujet comprenant les étapes consistant à :
    transmettre une troisième lumière au tissu, où la troisième lumière possède une troisième longueur d'onde supérieure à chacune des longueurs d'onde des lumières SO2,
    détecter une quantité de l'intensité lumineuse diffusée par le tissu à la troisième longueur d'onde à l'aide d'un second détecteur (328),
    déterminer le CBFi sur la base de la quantité d'intensité lumineuse détectée ;
    dans lequel le StO2 et le CBFi sont déterminés en même temps ;
    un filtre (316) est situé en face du premier détecteur, où le filtre permet aux lumières SO2 de passer au travers et atténue sensiblement la lumière de la troisième longueur d'onde.
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